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Paget disease of bone

Reviewed February 2010

What is Paget disease of bone?

Paget disease of bone is a disorder that causes bones to grow larger and weaker than normal. Affected bones may be misshapen and easily broken (fractured).

The classic form of Paget disease of bone typically appears in middle age or later. It usually occurs in one or a few bones and does not spread from one bone to another. Any bones can be affected, although the disease most commonly affects bones in the spine, pelvis, skull, or legs.

Many people with classic Paget disease of bone do not experience any symptoms associated with their bone abnormalities. The disease is often diagnosed unexpectedly by x-rays or laboratory tests done for other reasons. People who develop symptoms are most likely to experience pain. The affected bones may themselves be painful, or pain may be caused by arthritis in nearby joints. Arthritis results when the distortion of bones, particularly weight-bearing bones in the legs, causes extra wear and tear on the joints. Arthritis most frequently affects the knees and hips in people with this disease.

Other complications of Paget disease of bone depend on which bones are affected. If the disease occurs in bones of the skull, it can cause an enlarged head, hearing loss, headaches, and dizziness. If the disease affects bones in the spine, it can lead to numbness and tingling (due to pinched nerves) and abnormal spinal curvature. In the leg bones, the disease can cause bowed legs and difficulty walking.

A rare type of bone cancer called osteosarcoma has been associated with Paget disease of bone. This type of cancer probably occurs in less than 1 in 1,000 people with this disease.

Early-onset Paget disease of bone is a less common form of the disease that appears in a person's teens or twenties. Its features are similar to those of the classic form of the disease, although it is more likely to affect the skull, spine, and ribs (the axial skeleton) and the small bones of the hands. The early-onset form of the disorder is also associated with hearing loss early in life.

How common is Paget disease of bone?

Classic Paget disease of bone occurs in approximately 1 percent of people older than 40 in the United States. Scientists estimate that about 1 million people in this country have the disease. It is most common in people of western European heritage.

Early-onset Paget disease of bone is much rarer. This form of the disorder has been reported in only a few families.

What genes are related to Paget disease of bone?

A combination of genetic and environmental factors likely play a role in causing Paget disease of bone. Researchers have identified changes in several genes that increase the risk of the disorder. Other factors, including infections with certain viruses, may be involved in triggering the disease in people who are at risk. However, the influence of genetic and environmental factors on the development of Paget disease of bone remains unclear.

Researchers have identified variations in three genes that are associated with Paget disease of bone: SQSTM1, TNFRSF11A, and TNFRSF11B. Mutations in the SQSTM1 gene are the most common genetic cause of classic Paget disease of bone, accounting for 10 to 50 percent of cases that run in families and 5 to 30 percent of cases in which there is no family history of the disease. Variations in the TNFRSF11B gene also appear to increase the risk of the classic form of the disorder, particularly in women. TNFRSF11A mutations are responsible for the early-onset form of Paget disease of bone.

The SQSTM1, TNFRSF11A, and TNFRSF11B genes are involved in bone remodeling, a normal process in which old bone is broken down and new bone is created to replace it. Bones are constantly being remodeled, and the process is carefully controlled to ensure that bones stay strong and healthy. Paget disease of bone disrupts the bone remodeling process. Affected bone is broken down abnormally and then replaced much faster than usual. When the new bone tissue grows, it is larger, weaker, and less organized than normal bone. It is unclear why these problems with bone remodeling affect some bones but not others in people with this disease.

Researchers are looking for additional genes that may influence a person's chances of developing Paget disease of bone. Studies suggest that genetic variations in certain regions of chromosome 2, chromosome 5, and chromosome 10 appear to contribute to disease risk. However, the associated genes on these chromosomes have not been identified.

Related Gene(s)

Changes in these genes are associated with Paget disease of bone.

  • SQSTM1
  • TNFRSF11A
  • TNFRSF11B

How do people inherit Paget disease of bone?

In 15 to 40 percent of all cases of classic Paget disease of bone, the disorder has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that having one copy of an altered gene in each cell is sufficient to cause the disorder.

In the remaining cases, the inheritance pattern of classic Paget disease of bone is unclear. Many affected people have no family history of the disease, although it sometimes clusters in families. Studies suggest that close relatives of people with classic Paget disease of bone are 7 to 10 times more likely to develop the disease than people without an affected relative.

Early-onset Paget disease of bone is inherited in an autosomal dominant pattern. In people with this form of the disorder, having one altered copy of the TNFRSF11A gene in each cell is sufficient to cause the disease.

Where can I find information about diagnosis or management of Paget disease of bone?

These resources address the diagnosis or management of Paget disease of bone and may include treatment providers.

  • Genetic Testing Registry: Osteitis deformans (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0029401)
  • MedlinePlus Encyclopedia: Paget's Disease of the Bone (http://www.nlm.nih.gov/medlineplus/ency/article/000414.htm)

You might also find information on the diagnosis or management of Paget disease of bone in Educational resources (http://www.ghr.nlm.nih.gov/condition/paget-disease-of-bone/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/paget-disease-of-bone/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Paget disease of bone?

You may find the following resources about Paget disease of bone helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Paget disease of bone?

  • osseous Paget's disease
  • osteitis deformans
  • Paget disease, bone
  • Paget's disease of bone
  • PDB

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Paget disease of bone?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Paget disease of bone?

arthritis ; autosomal ; autosomal dominant ; bone remodeling ; cancer ; cell ; chromosome ; family history ; gene ; inheritance ; inheritance pattern ; inherited ; osteoclast ; osteosarcoma ; pattern of inheritance ; pelvis ; phosphatase ; tissue ; x-rays

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Daroszewska A, Ralston SH. Mechanisms of disease: genetics of Paget's disease of bone and related disorders. Nat Clin Pract Rheumatol. 2006 May;2(5):270-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16932700?dopt=Abstract)
  • Goode A, Layfield R. Recent advances in understanding the molecular basis of Paget disease of bone. J Clin Pathol. 2010 Mar;63(3):199-203. doi: 10.1136/jcp.2009.064428. Epub 2009 Oct 26. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19858527?dopt=Abstract)
  • Hageman GS, Kirchoff-Rempe MA, Lewis GP, Fisher SK, Anderson DH. Sequestration of basic fibroblast growth factor in the primate retinal interphotoreceptor matrix. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6706-10. (http://www.ncbi.nlm.nih.gov/pubmed/1862095?dopt=Abstract)
  • Langston AL, Campbell MK, Fraser WD, MacLennan GS, Selby PL, Ralston SH; PRISM Trial Group. Randomized trial of intensive bisphosphonate treatment versus symptomatic management in Paget's disease of bone. J Bone Miner Res. 2010 Jan;25(1):20-31. doi: 10.1359/jbmr.090709. (http://www.ncbi.nlm.nih.gov/pubmed/19580457?dopt=Abstract)
  • Lucas GJ, Daroszewska A, Ralston SH. Contribution of genetic factors to the pathogenesis of Paget's disease of bone and related disorders. J Bone Miner Res. 2006 Dec;21 Suppl 2:P31-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17229006?dopt=Abstract)
  • Ralston SH, Langston AL, Reid IR. Pathogenesis and management of Paget's disease of bone. Lancet. 2008 Jul 12;372(9633):155-63. doi: 10.1016/S0140-6736(08)61035-1. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18620951?dopt=Abstract)
  • Ralston SH. Juvenile Paget's disease, familial expansile osteolysis and other genetic osteolytic disorders. Best Pract Res Clin Rheumatol. 2008 Mar;22(1):101-11. doi: 10.1016/j.berh.2007.11.005. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18328984?dopt=Abstract)
  • Ralston SH. Pathogenesis of Paget's disease of bone. Bone. 2008 Nov;43(5):819-25. doi: 10.1016/j.bone.2008.06.015. Epub 2008 Jul 11. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18672105?dopt=Abstract)
  • Whyte MP. Clinical practice. Paget's disease of bone. N Engl J Med. 2006 Aug 10;355(6):593-600. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16899779?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: February 2010
Published: October 9, 2014